Candida meningitis in two children with severe combinedimmunodeficiency

Fungal infections of the central nervous system (CNS) are life-threatening conditions that generally involve an immunosuppressive event. Many of these infections occur sporadically in the course of a serious underlying disease. However, outbreaks of CNS fungal disease may occur, as exemplified by the Cryptococcus gattii infections in British Columbia and the northwest United States and by iatrogenic paraspinal infection after injection of contaminated corticosteroids. The clinician must be aggressive in diagnosing these infections and then use either robust treatment guidelines or simply expert opinion to determine appropriate management. These serious infections remain a major challenge in the clinical management of a vulnerable host population.

Both acquired and congenital immunodeficiencies may be associated with increased susceptibility to invasive fungal infections (IFIs), depending on the type of immune deficit. IFIs frequently occur in patients with phagocytic and cellular immune defects, but are rarely observed in those with humoral or complement deficits. Among congenital immune disorders, chronic granulomatous disease and hyper-IgE syndrome are most frequently associated with IFIs; variable susceptibility to fungal pathogens is also seen in patients with severe combined immunodeficiency, X-linked hyper-IgM syndrome, Wiskott–Aldrich syndrome, DiGeorge syndrome, common variable immunodeficiency, defects in the interferon-γ–interleukin-12 axis, and myeloperoxidase deficiency. Aspergillus, Candida, Cryptococcus, Histoplasma and other fungal genera are variably implicated in causing invasive infections in these patients. Prompt diagnosis of IFIs in this patient population requires a high degree of suspicion, together with a knowledge of their clinical presentation and the limitations of diagnostic modalities. Apart from administration of appropriate antifungal agents, successful management often requires the addition of surgical intervention. Adjunctive immunotherapy may be considered, although this has not been systematically studied. Prophylactic interferon-γ and itraconazole administration have been shown to reduce the risk of IFIs in patients with chronic granulomatous disease; however, the possibility of infections with azole-resistant organisms following long-term itraconazole prophylaxis should not be overlooked.

In this paper we have reviewed the main clinico-pathologic disease groups of neurocandidiasis: the microabscesses, the macroabscesses, and the meningitis. Special attention has been paid to the predisposing conditions for the appearance of neurocandidiasis, the neuroimaging techniques, and the study of the cerebrospinal fluid, needed for diagnosis. We have also discussed the differential diagnosis with other illnesses. Treatment should be given with amphotericin-B and 5-fluorocytosine. The use of other antifungal drugs for neurocandidiasis is also discussed.

Infection still remains the most common immediate cause of death in the immunocompromised host. Because of the decreased host defenses leading not only to an increased susceptibility to a variety of opportunistic pathogens (in particular the fungi) but also to a decreased host inflammatory response and resultant clinical findings, infections in these patients are difficult to diagnose. Skin lesions occur in up to a third of infections in compromised hosts and can often be the first presentation of a systemic illness. The broad scope of dermatologic manifestations of infection in compromised patients is reviewed based on four presumed underlying pathophysiologic mechanisms and on the vast array of potential pathogens that have been reported to date in the literature.